Knowing why some embryos implant and others not is a challenge that should be overcome in the field of reproductive medicine. The intimate knowledge of physiological aspects of this process is important to design strategies that allow increasing the chance of pregnancy.
The various sections of this article are assembled in the following table of contents.
Only one third of cycles considered as fertile result in pregnancy. The cause of this low pregnancy rate is due to several factors such as an inappropriate uterine environment, since it should be a favorable hormonal environment (estradiol and progesterone), a poor embryo quality, a low maternal endometrial receptivity and a defective dialogue between them (embryo and endometrium).
Clinical gestation rate per menstrual cycle is 25-30% in couples considered fertile who usually have regular sexual intercourse without birth control. This is a relatively low rate in comparison with other animal species, although it is cumulative, that is to say, it increases month by month reaching 80% after ten months.
Implantation treatment has been limited to the use of luteal phase protocols by the administration of progesterone and hCG (human chorionic gonadotropin) for years. Nowadays various basic and clinic studies on this subject have allowed knowing which role the different cell populations of the uterus play in implantation and the rol of some molecules such as cytokines, integrins, adhesion molecules and growth factors.
There is some evidence that cytokines and growth factors play an important role as local mediators of steroid hormones actions on the endometrium, with the objective of preparing it for the implantation. It is believed that signs coming from preimplantation embryo could lead to cytokine production through the endometrium, in turn and by connecting it to membrane specific receptors, which would activate adhesion molecule expression such as integrins, which are in charge of blastocyst adhesion to the endometrium.
Biologically, it is a complex process where an embryo in blastocyst stage is settled in the mother’s receptive endometrium. There must be perfect synchrony between the embryo and the endometrium.
Implantation takes place in the middle third of the posterior face of the uterus and it happens during a specific period of time in which this dialogue between embryo and mother is possible. This moment is called implantation window and it ranges between day 20 to 24 of menstrual cycle (about six or seven days after fertilisation).
Implantation window is the moment when the receptive endometrium allows the adhesion of the blastocyst. This change from non-receptive to receptive endometrium only happens if there is an appropriate hormonal environment and if the blastocyst express adequate molecules to induce the change (selectins, cytokines, etc.).
Implantation consists of three stages: apposition, adhesion and invasion.
The blastocyst looks for a place to implant, a place where blastocyst adheres orienting its inner cell mass to the pole in which the trophectoderm is going to adhere to the endometrial epithelium.
In this case the so-called pinopodes (cytoplasmic projections of epithelial endometrial cells) play an important role, since they help the blastocyst to come into contact with the endometrial epithelium.
It is proved that these pinopodes are clear morphological signs of endometrial receptivity, they only appear during the implantation window and will disappear about day 24 of menstrual cycle.
The blastocyst adheres to endometrial epithelium, it remains fixed. This happens six or seven days after fertilisation, when the blastocyst has a diameter of 300-400 µm. Throughout this process, cytokines have much to do with, more specifically, chemokines.
The blastocyst (more specifically, embryonic trophoblast) invades the endometrial stroma, breaks the basal membrane and penetrates into the maternal blood vessels. Trophoblastic cells move, dissociate and replace epithelial cells, they continue to invade the basal membrane and the underlying stroma.
Although at first sight it may seem easy that a blastocyst implants in the maternal endometrium, this is a complex process which is still not fully understood.
Within in vitro fertilisation, implantation is one of the most delicate and crucial moments for achieving pregnancy and, since it cannot be externally controlled, it depends on circumstances surrounding the patient such as embryo quality, endometrial receptivity, the time of transfer and a perfect synchrony between all these factors.